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Comparison of expression profiles of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells

ABSTRACT: Analysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation. GFP+CD4+ and GFP-CD4+ splenocytes were sorted from DEREG and DEREG/Scurfy mice. These cells were activated with anti-CD3/CD28 antibodies, and then transduced with Foxp3-expressing retrovirus (pGCSamIN, NGFR marker). NGFR+ T cells sorted were subjected to microarray analysis (Affymetrix, mouse genome 430 2.0 array). To normalize the experimental conditions, Tregs (GFP+ T cells from DEREG) and Tconv (GFP- T cells from DEREG) were also activated and transduced with empty vector. Two replicates each.

ORGANISM(S): Mus musculus  

SUBMITTER: Hiromasa Morikawa  

PROVIDER: E-GEOD-25252 | ArrayExpress | 2012-11-05



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T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.

Ohkura Naganari N   Hamaguchi Masahide M   Morikawa Hiromasa H   Sugimura Kyoko K   Tanaka Atsushi A   Ito Yoshinaga Y   Osaki Motonao M   Tanaka Yoshiaki Y   Yamashita Riu R   Nakano Naoko N   Huehn Jochen J   Fehling Hans Joerg HJ   Sparwasser Tim T   Nakai Kenta K   Sakaguchi Shimon S  

Immunity 20121101 5

The transcription factor Foxp3 is essential for the development of regulatory T (Treg) cells, yet its expression is insufficient for establishing the Treg cell lineage. Here we showed that Treg cell development was achieved by the combination of two independent processes, i.e., the expression of Foxp3 and the establishment of Treg cell-specific CpG hypomethylation pattern. Both events were induced by T cell receptor stimulation. The Treg cell-type CpG hypomethylation began in the thymus and cont  ...[more]

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